Constitutive Production and Release of a Lymphokine with Macrophage-activating Factor Activity Distinct from γ -lnterferon by a Human T-Cell Leukemia Virus-positive Cell Line

Culture supernatant fluids from the human T-cell leukemia viais-positive cell line C10/MJ-2 were found to contain a soluble factor with macrophage-activating factor (MAF) activity. The MAF activity of this culture supernatant fluid was stable at 100° for 2 min and was unaffected by treatment with human anti-γ -interferon (IFN-γ ) monoclonal antibody. Both treatments neutralized >97% IFN-γ activity from the supernatant fluid as measured by virus neutralization. Furthermore, this MAF activity was not due to contamination with endotoxins since the Umulus amebocyte lysate assay was negative (<0.125 ng/ml) and preincubation of the C10/MJ-2 supernatant fluid with polymyxin B did not diminish its activating potential. By contrast, human IFN-γ rendered human monocytes tumoricidal only when combined with Salmonella typhosa lipopoiysaccharide (LPS) at a minimum dose of 0.2 ng/ ml. The concentrations of both LPS and IFN-γ were crucial to achieve activation since IFN-γ at doses <10 units/ml did not activate human monocytes even when combined with maximal doses of LPS (0.5 ng/ml). Finally, when human IFN-γ admixed with LPS was preincubated with polymyxin B, its activating potential was completely abrogated. Collectively, these data suggest that the human T-cell line C10/MJ-2 constitutively produces a diffusabie product distinct from IFN-γ which activates human monocytes to lyse tumor cells. Thus, this cell line could provide a good source of a unique human MAF for future purification procedures.